Facilitation of transcutaneous drug delivery and vaccine immunization by a safe laser technology

• Published in: Journal of controlled release Vol. 159; no. 1; pp. 43 - 51
• Main Authors: Chen, Xinyuan, Shah, Dilip, Kositratna, Garuna, Manstein, Dieter, Anderson, Richard R., Wu, Mei X.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 10.04.2012; Elsevier
• Subjects: Administration, Cutaneous; Animals; Antigens - administration & dosage; Biological and medical sciences; Controlled release; Data processing; Dendritic cells; Dermis; Drug; Drug delivery; Drug Delivery Systems; General pharmacology; hydrophilicity; Hydrophobic and Hydrophilic Interactions; immune response; Immunization; Immunization - instrumentation; Immunization - methods; Immunosuppressive agents; Langerhans cells; Laser; Laser Therapy - methods; Lasers; Lymph nodes; Male; Medical sciences; Methylene blue; Methylene Blue - administration & dosage; Mice; Mice, Inbred BALB C; Ovalbumin; Ovalbumin - administration & dosage; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rhodamines - administration & dosage; Self; Skin; Skin - metabolism; Skin - pathology; Stratum corneum; sulforhodamine; Tape stripping; Transcutaneous delivery; Transdermal patch; Vaccine; Vaccines; Drug; Tape stripping; Vaccine; Transcutaneous delivery; Transdermal patch; Laser; Delivery system; Immunization; Pharmaceutical technology; Drug carrier; Adhesive tape; Percutaneous route; Dosage form; Patch
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.01.002

Full-surface laser ablation has been shown to efficiently disrupt stratum corneum and facilitate transcutaneous drug delivery, but it is frequently associated with skin damage that hampers its clinic use. We show here that a safer ablative fractional laser (AFL) can sufficiently facilitate delivery of not only patch-coated hydrophilic drugs but also protein vaccines. AFL treatment generated an array of self renewable microchannels (MCs) in the skin, providing free paths for drug and vaccine delivery into the dermis while maintaining integrity of the skin by quick healing of the MCs. AFL was superior to tape stripping in transcutaneous drug and vaccine delivery as a much higher amount of sulforhodamine B (SRB), methylene blue (MB) or a model vaccine ovalbumin (OVA) was recovered from AFL-treated skin than tape-stripped skin or control skin after patch application. Following entry into the MCs, the drugs or OVA diffused quickly to the entire dermal tissue via the lateral surface of conical-shaped MCs. In contrast, a majority of the drugs and OVA remained on the skin surface, unable to penetrate into the dermal tissue in untreated control skin or tape stripping-treated skin. Strikingly, OVA delivered through the MCs was efficiently taken up by epidermal Langerhans cells and dermal dendritic cells in the vicinity of the MCs or transported to the draining lymph nodes, leading to a robust immune response, in sharp contrast to a weak, though significant, immune response elicited in tape stripping group or a basal immune response in control groups. These data support strongly that AFL is safe and sufficient for transcutaneous delivery of drugs and vaccines. A safe ablative fractional laser (AFL) creates conical-shaped microchannels that allow sufficient drug/vaccine delivery, resulting in a vigorous potent immune response as compared to tape stripping and control. [Display omitted]